Hydroxycarboxylic acids, and in particular carbohydrate diacids (aldaric acids) offer significant economic potential as carbon based chemical building blocks for the chemical industry, as safe additives or components of products used in pharmaceutical preparations and food products, and as structural components of biodegradable polymers, if they can be effectively produced on an industrial scale. Glucaric acid, for example, is produced through the oxidation of glucose and in salt form is currently in use as a nutraceutical for preventing cancer. The price of this material however is high, approximately $100/lb. Industrial scale production of aldaric acids would also provide sufficient materials for the production of other useful compounds, that include environmentally degradable polyamides with varying properties and applications, which are otherwise not commercially available.
Carbohydrate diacids are produced a number of ways from reducing sugars using a variety of oxidizing agents, including nitric acid. An example of a nitric acid oxidation of a carbohydrate is that of D-glucose to give D-glucaric acid, typically isolated as its mono potassium salt (See, W. N. Haworth and W. G. M. Jones, J. Chem. Soc., 65-76 (1944), C. L. Mehltretter and C. E. Rist, Agric. and Food Chem., 1, 779-783 (1953) and C. L. Mehltretter, “D-Glucaric Acid”, in Methods in Carbohydrate Chemistry, R. L. Whistler, M. L. Wolfrom, Eds; Academic Press, New York, 1962, Vol. II, pp 46-48). Alternatively, D-glucaric acid can be isolated from nitric acid oxidation of D-glucose as a disodium salt (See, D. E. Kiely, A. Carter and D. P. Shrout, U.S. Pat. No. 5,599,977, Feb. 4, 1997) or as the 1,4:6,3-dilactone (See, D. E. Kiely and G. Ponder, U.S. Pat. No. 6,049,004, Apr. 11, 2000). Routes have been described showing synthesis of diacids through catalytic oxidation with oxygen over a noble metal catalyst (See, C. L. Mehltretter, U.S. Pat. No. 2,472,168, Jun. 7, 1949). An additional route of synthesis exists by use of oxoammonium salts in combination with hypophalites as the terminal oxidants. For example, Merbough and coworkers describe oxidation of D-glucose, D-mannose and D-galactose to their corresponding diacids using 4-acetylamino-2,2,4,6-tetamethyl-1-piperidinyloxy (4-AcNH-TEMPO) with hypohalites as the oxidizing medium (See, N. Merbough, J. M. Bobbitt and C. Bruckner, J. Carbohydr. Chem., 21, 66-77 (2002) and Merbouh, J M. Bobbitt, and C. Bruckner, U.S. Pat. No. 6,498,269, Dec. 24, 2002). A microbial oxidation of myo-inositol to glucuronic acid which is then oxidized enzymatically or by catalytic oxidation to glucaric acid has also been recently described (See, W. A. Schroeder, P. M. Hicks, S. McFarlan, and T. W. Abraham, U.S. Patent Application, 20040185562, Sep. 24, 2004).
A variety of different processes for the oxidation of carbohydrates using nitric acid are known. For example, U.S. Pat. No. 2,380,196 (the '196 patent) describes the nitric acid oxidation of carbohydrates to dibasic acids, particularly tartaric acid. The '196 patent describes a cyclic process in which in each cycle, fresh carbohydrate and residue from a previous oxidation is oxidized with nitric acid. A catalyst, such as vanadium, manganese, iron and molybdenum, is employed to increase the yield of tartaric acid. According to the '196 patent, good yields are obtained when the molar ratio of nitric acid to glucose is 5:7.5, preferably 6:7.5. The '196 patent also describes that when mixing the ingredients, the temperature should be maintained at 20° C. or lower. Following mixing, the temperature is raised gradually or allowed to rise spontaneously to about 30° C. to 35° C. (this is the induction or heating-up stage). When the temperature reaches 30° C. to 35° C., an autocatalytic strong exothermic reaction called the “blow” sets in. The “blow” stage is maintained at a temperature of about 50° C. to 75° C., preferably 65-70° C. for anywhere from 45 to 120 minutes. The final temperature stage of the oxidation is the “fume-off” stage at which the last of the nitric acid is reacted and passed off as lower nitrogen oxides. During the “fume-off” stage, the reaction mixture is maintained at a high temperature somewhat below the boiling point of the mixture, at approximately 90° C. to 95° C. until nitrogen oxide is no longer detectable by the fumes. Oxalic and tartaric acids are recovered from the oxidized reaction mixture by direct precipitation and crystallization.
U.S. Pat. No. 2,436,659 (the '659 patent) discloses an improved and economical process for the production of D-saccharic acid. Specifically, the '659 patent discloses a process that produces higher yields of D-saccharic acid in a shorter period of time, is more convenient while not employing the use of metal oxidation catalysts. According to the '659 patent, crystalline D-glucose, in anhydrous or monohydrate form, is added to a solution of nitric acid at a rate that allows control of the temperature of the reaction between 55° C. to 90° C. The mole ratio of glucose to nitric acid used in the process is 1:4. However, the '659 patent notes that a mole ratio of glucose to nitric acid of 1:3 lowers the yield of D-saccharic acid while a ratio of 1:8 increases this yield. The '659 patent also discloses that when 60 to 70 percent nitric acid is used it is preferred to use reaction temperatures of 55° C. to 70° C. and that when lower concentrations of nitric acid are employed higher reaction temperatures are preferred. When the process is performed in this manner, it is quite rapid, with maximum yields of D-saccharic acid being obtained in a one-hour period of oxidation.
U.S. Pat. No. 3,242,207 (the '207 patent) discloses a continuous process for the oxidation of D-glucose with nitric acid at elevated temperatures. Specifically, the process described in the '207 patent is performed as follows: (1) to an initial reaction mixture prepared by oxidizing an aqueous solution of D-glucose with concentrated nitric acids, an aqueous D-glucose solution and concentrated nitric acid in the molecular ratio of 1:3 to 1:3.5 is simultaneously and continuously added at a temperature of about 40° C. to 70° C.; (2) continuously withdrawing from the reaction vessel an apportion of the reaction mixture corresponding to the volume of the fed-in liquids; and (3) isolating the product formed.
U.S. Pat. No. 7,692,041 (the '041 patent) discloses an improved method for oxidizing water soluble compounds using nitric acid oxidation. The method involves (1) preparing an aqueous solution of an organic compound suitable for nitric acid oxidation; (2) combining, over time, employing a controlled process, in a closed reaction vessel, under positive pressure of oxygen, the aqueous solution of the organic compound and an aqueous solution of nitric acid to oxidize the organic compound to a mixture of organic acids; (3) maintaining controlled, moderate temperatures of from about 25° C. to about 50° C., controlled positive pressure of oxygen, and controlled agitation of the organic compound and nitric acid reaction mixture during the oxidation reaction; and (4) removing a portion of the nitric acid from the combined aqueous solution to give a mixture of organic acids suitable for further processing.
There is a need in the art for improved oxidation process that is safe, economical and efficient for converting organic compounds into their corresponding acids.